title: Comparative effects of prolonged and intermittent stimulation of the glucagon-like peptide 1 receptor on gastric emptying and glycemia.
abstract: Acute administration of glucagon-like peptide 1 (GLP-1) and its agonists slows gastric emptying, which represents the major mechanism underlying their attenuation of postprandial glycemic excursions. However, this effect may diminish during prolonged use. We compared the effects of prolonged and intermittent stimulation of the GLP-1 receptor on gastric emptying and glycemia. Ten healthy men received intravenous saline (placebo) or GLP-1 (0.8 pmol/kg ⋅ min), as a continuous 24-h infusion ("prolonged"), two 4.5-h infusions separated by 20 h ("intermittent"), and a 4.5-h infusion ("acute") in a randomized, double-blind, crossover fashion. Gastric emptying of a radiolabeled mashed potato meal was measured using scintigraphy. Acute GLP-1 markedly slowed gastric emptying. The magnitude of the slowing was attenuated with prolonged but maintained with intermittent infusions. GLP-1 potently diminished postprandial glycemia during acute and intermittent regimens. These observations suggest that short-acting GLP-1 agonists may be superior to long-acting agonists when aiming specifically to reduce postprandial glycemic excursions in the treatment of type 2 diabetes.
authors.affiliation: Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Mahesh M
authors.initials: MM
authors.lastname: Umapathysivam
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Lee
authors.forename: Karen L
authors.initials: KL
authors.lastname: Jones
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Annink
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Cousins
authors.forename: Laurence G
authors.initials: LG
authors.lastname: Trahair
authors.forename: Chris K
authors.initials: CK
authors.lastname: Rayner
authors.forename: Marianne J
authors.initials: MJ
authors.lastname: Chapman
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nauck
authors.forename: Michael
authors.initials: M
authors.lastname: Horowitz
authors.forename: Adam M
authors.initials: AM
authors.lastname: Deane
mesh_terms: D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005746:Gastric Emptying / Q000502:physiology*; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000494:pharmacology*; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D018027:Receptors, Glucagon / Q000378:metabolism*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D005947:Glucose